All About Pediatric Non-Hodgkin Lymphoma
Ben Oshrine, MD
The Children's Hospital of Philadelphia
Last Modified: April 17, 2013
What is lymphoma?
In general, lymphoma is a type of cancer affecting cells of the lymph system. The lymph system is part of the immune system that consists of a network of lymph nodes, lymph vessels, and organs, including the thymus, spleen, and bone marrow. Lymphoma can arise from any of these tissues. There are two broad categories of lymphoma: non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma, which is discussed in a separate article. The cancerous cell in NHL is called a "lymphocyte", which is a cell that ordinarily is involved in the immune response that protects the body from infection. In NHL, these lymphocytes divide at an abnormally fast rate causing enlargement of lymph nodes or other organs in the lymph system and are responsible for the symptoms experienced by children with NHL.
Who is at risk for NHL?
As for most childhood cancers, the majority of pediatric cases of NHL occur in patients without specific risk factors, or "sporadically". In the absence of risk factors, NHL tends to affect adolescent and young adult patients more than young children. In a small minority of cases, NHL occurs in patients who have a predisposing condition or risk factor for developing this specific form of cancer. The most common risk factor in pediatric patients is immunodeficiency, because of either an inherited or acquired condition affecting the immune system. A variety of inherited immunodeficiencies can predispose to developing NHL, but all are rare conditions. Acquired immunodeficiencies can occur when children require medications that suppress certain immune cells, such as after receiving a solid organ transplant (e.g. kidney, liver, heart, lung) to prevent graft rejection, or in the case of viruses such as HIV.
What Are the Symptoms of NHL?
Children can experience a very wide range of symptoms when affected by NHL, depending on where in the body the lymphoma cells are present. Below is a list of some of the more common symptoms that can lead a physician to suspect NHL:
- Enlarged lymph nodes in the neck, underarm, or groin (usually painless and firm)
- Enlarged spleen or liver
- Difficulty breathing or cough (from an enlarged thymus—an immune organ in the upper chest)
- Unexplained fevers, unintentional weight loss, or sweating profusely at night
- Vomiting or abdominal pain—caused by obstruction from enlarged lymph nodes in the intestines
How is NHL Diagnosed?
When a child has symptoms that suggest a diagnosis of NHL, his/her physician will conduct a history and physical examination. While the usual next step in the evaluation is to obtain basic laboratory and imaging tests, these do not provide a definite diagnosis. Findings from this initial evaluation help to determine how and where to obtain a tissue sample, or biopsy, which is necessary in order to definitively diagnose NHL. If an enlarged lymph node is present, this will be removed and examined, under a microscope, by a pathologist. If special tests need to be conducted on the biopsy it may take several days or longer to confirm a diagnosis of NHL.
NHL is categorized based on the specific type of lymphocyte that has become cancerous, and its stage of maturation. Each type of NHL behaves somewhat differently in response to therapy, and knowing the specific subtype allows more precise treatment approaches. In general, the types of NHL that affect children divide rapidly and are considered aggressive, making them very amenable to treatment because chemotherapy works by killing rapidly dividing cells. The following are the major types of NHL seen in pediatric patients:
- Burkitt lymphoma
- Diffuse large B cell lymphoma (DLBCL)
- Anaplastic large cell lymphoma
- Lymphoblastic lymphoma (either T- or B-cell)
There are many other types of NHL, but most of these are seen primarily in adults and rarely affect children.
How is NHL Staged?
Once the diagnosis of NHL is established, a pediatric oncologist (doctor specializing in the care of children with cancer) will conduct a staging evaluation. In general, patients with NHL will undergo the following tests to determine where else in the body NHL cells may be and to test how well other organs in the body are working:
- Laboratory evaluation of blood counts, electrolytes & kidney/liver function
- CT scan of neck, chest, abdomen, and pelvis
- Positron emission tomography (PET) scan—a type of CT that identifies areas in the body with a high metabolic rate, like cancer
- Bone marrow sampling
- Cerebrospinal fluid sampling by lumbar puncture (spinal tap)
This battery of tests will accurately characterize the extent of disease (stage), which will help the oncologist decide what type of treatment is needed, and provide a useful baseline to measure response to treatment in the future. NHL is staged using the St. Jude system:
- Stage I: single site of disease (not in chest or abdomen)
- Stage II: 2 or more lymph node groups on same side of diaphragm
- Stage III: 2 or more lymph node groups on opposite sides of the diaphragm; or any chest tumor or tumor near the spinal cord
- Stage IV: involvement of the spinal fluid and/or bone marrow
How is NHL treated?
Knowing the specific subtype of NHL and the staging information is critical for formulating an effective treatment plan. In general, this information is obtained prior to initiating any therapy. In situations where the cancer is the cause of a medical emergency, however, urgent treatment may begin prior to having all the necessary information. Examples of such emergencies include times when the lymphoma is threatening the function of a vital organ or structure such as the heart, airway, spinal cord, or kidneys, or when the rapidly dividing lymphoma cells are causing serious disturbances in the electrolyte balances in the body. These situations are relatively uncommon.
Because the vast majority of NHLs affecting children are composed of rapidly dividing and aggressive lymphoma cells, chemotherapy is a very effective treatment modality for pediatric NHL. In fact, surgery and radiation are no longer standard components of the initial therapy of NHL because most patients respond very quickly to chemotherapy. The type of chemotherapy depends entirely on the subtype of NHL and the extent of disease (staging), and varies both in terms of the intensity and duration of treatment. In all cases, combinations of drugs are used to attack the lymphoma in multiple different ways.
For Burkitt lymphoma and DLBCL, treatment tends to be short (lasting 3-6 months) but intensive. Anaplastic large cell lymphoma therapy is somewhat longer (up to 1 year) but almost entirely outpatient. Finally, lymphoblastic lymphomas are treated mostly as outpatients over approximately 2 years. Since the style and duration of chemotherapy differs dramatically based on the subtype of NHL, it is difficult to generalize what specific chemotherapy agents are used; however, some of the more common medications used (in combination) to treat pediatric NHL are:
- Steroids (prednisone, prednisolone, dexamethasone)
- Cytarabine (Ara-c)
Depending on the subtype of NHL and whether the lymphoma is present in the cerebrospinal fluid, chemotherapy may be administered directly into the spinal fluid during a lumbar puncture. This is called intrathecal chemotherapy and is given along with standard chemotherapy. Sometimes, even when lymphoma cells are not seen in the spinal fluid during the initial staging evaluation, intrathecal chemotherapy is used preventatively to decrease the risk of the lymphoma coming back in the central nervous system.
One of the most important aspects of the treatment process is monitoring the individual patient's response. While we know what medicines work for most children with NHL, currently we cannot predict with complete certainty which lymphomas will respond. During treatment, the oncologist will get imaging tests (mostly CT scans and sometimes PET scans) to evaluate how well the lymphoma is responding. If the response is slow or not complete, changes to the treatment plan may be made to see if alternative chemotherapy agents will be effective.
How effective is treatment for NHL?
The majority of NHL affecting children will be cured. Exact percentages achieving cure depend on the subtype of NHL and the extent of disease. In general, lymphomas that are more extensive (higher stage) are more difficult to cure. In addition, response to therapy is strongly predictive of outcome, and those children whose NHL does not respond to standard initial therapy are more challenging to cure.
What if NHL comes back after treatment
After therapy is over, children who have been treated for NHL are monitored every several months with labs, imaging tests, and physical examinations to determine if the lymphoma is coming back (relapsing). The highest risk for relapse is in the first two years after the end of treatment, but can occur later. Relapsed NHL is more difficult to cure than initial NHL, and typically involves more intensive therapy—often with different medications than those used initially. If another remission is achieved, many patients will require a bone marrow transplant and radiation to optimize their chance of cure. The bone marrow transplant will either use the patient's own cells to help them recover from very high doses of chemotherapy (autologous transplant) or bone marrow cells from another person (allogeneic transplant). The choice of whether to use bone marrow transplant and which type is appropriate is highly individualized, and depends on the subtype of NHL, the timing of relapse, response to treatment, availability of donors, among many others.
References & Further Reading
Orkin, Stuart et al. Oncology of Infancy and Childhood. Philadelphia: Saunders, 2009. Print.
National Cancer Institute: Childhood NHL